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Study Published Showing Advantages of the PAM50 Gene Signature, the Basis for Prosigna, in Helping to Estimate Risk of Late Distant Recurrence in Postmenopausal Estrogen Receptor Positive Breast Cancer Patients

NanoString Technologies, Inc., (NASDAQ: NSTG) a provider of life science tools for translational research and molecular diagnostic products, recently announced that a study published online in the Journal of the National Cancer Institute demonstrated that the PAM50 gene signature, which is the basis for the Prosigna™ Breast Cancer Prognostic Gene Signature Assay, provides important information to help estimate the risk of late distant recurrence in postmenopausal women with estrogen receptor positive (ER+) early-stage breast cancer. After comparing the PAM50 gene signature, the Oncotype DX® Breast Cancer Assay and the IHC4 score, the authors concluded that the PAM50 gene signature provided the strongest prognostic information regarding risk of distant recurrence five to 10 years following diagnosis in postmenopausal ER+ early-stage breast cancer patients treated with five years of endocrine therapy.

Exosome Diagnostics Enters Collaboration Agreement with Lilly for Exosome Blood-Based Biomarker Discovery

Exosome Diagnostics recently announced it has entered into a collaboration agreement with Eli Lilly and Company (NYSE: LLY) for biomarker discovery and validation using Exosome Diagnostics proprietary EXO50 nucleic acid extraction kit. Under the agreement, Lilly will gain early access to Exosome Diagnostics technology to help identify key gene mutations and expression levels in blood that may be correlated with drug response and disease recurrence. Financial terms were not disclosed.

“Exosome Diagnostics technology may provide a unique opportunity to gain insight into the biology of complex conditions such as cancer and immune disorders,” said Andrew Schade, senior medical director, diagnostic and experimental pathology at Lilly. “Exosome technology enables biofluid molecular sampling and the ability to monitor disease progression in real time. As Lilly explores new ways to pursue patient tailoring, we’ll continue to work with partners to expand our capabilities.”

“Accessing high quality messenger and microRNA directly from frozen patient fluid samples offers a rapid, cost-effective route to identify and validate biomarkers, which may be correlated with drug response and disease recurrence,” said James McCullough, chief executive officer of Exosome Diagnostics. “Lilly has accumulated an extensive and well annotated clinical blood sample biobank that provides a unique opportunity to track target biomarkers through the clinical trial process and help overcome the limitations of stored biopsy tissue.”

Exosomes and other microvesicles are secreted by all cells into all biofluids, and provide a natural biological packaging and distribution mechanism for RNA and DNA. Exosome Diagnostics’ rapid exosome isolation and extraction technology produces high-quality RNA and DNA, including full length mRNA and microRNA, from small volumes of patient biofluids, such as blood (serum and plasma), urine and cerebrospinal fluid, for analysis by standard PCR, array and sequencing instruments. Analysis can be performed on fresh or frozen fluid samples, allowing for broad, flexible and convenient analyses of clinical trial samples, both in real-time and retrospectively, with no special preservation methods required. Exosomes and their protected nucleic acid contents are being investigated in a broad range of diseases including cancer, CNS disorders such as Alzheimer’s and Parkinson’s disease, cardiovascular disease, maternal/fetal medicine, and chronic kidney disease, among others. In July, QIAGEN and Exosome Diagnostics signed an agreement for the creation of High-Performance Biofluid Sample Preparation Kits for Personalized Healthcare Research which covers the exclusive supply of these products upon availability in 2014.

Source: Exosome Diagnostics

AB SCIEX Proteomics Scientist Wins HUPO 2013 Science and Technology Award

The Human Proteome Organization (HUPO) recently awarded Christie Hunter, Ph.D, director of proteomics applications at AB SCIEX, its 2013 Science and Technology Award at an award ceremony during last week’s HUPO 2013 conference in Japan. Dr. Hunter was recognized for her contributions to the development and commercialization of a breakthrough approach for targeted proteomics. The analytical strategy of targeted proteomics was recently named “Method of the Year” by Nature Methods.

Targeted proteomics is a standardized, biological research workflow that focuses on reproducibly quantifying a specific subset of proteins within a sample. It generates data that is vital for biologists to answer hypothesis-driven, biological questions.

A decade ago, proteomics research was dominated by discovery workflows, which provided valuable information on a single sample but lacked the reproducibility to generate robust quantitation across a larger sample set. New innovation was needed at the time to move the field beyond simply producing large lists of identified proteins and toward providing highly quantitative answers.

This led to the development of a multiple reaction monitoring (MRM)-triggered, tandem mass spectrometry (MS/MS) workflow at AB SCIEX to rapidly create high sensitivity MRM assays to target peptides that are unique to their associated proteins. This workflow was made possible by the combination of triple quadrupole and linear ion trap functionality in a single system called the AB SCIEX QTRAP® System.

Dr. Hunter ‒ in collaboration with researcher Dr. Leigh Anderson, the founder of the Plasma Proteome Institute and head of SISCAPA Assay Technologies ‒ pioneered a workflow that applied MRM to the targeted quantification of proteins and peptides in plasma by mass spectrometry. In their initial publication[1], Dr. Hunter and Dr. Anderson demonstrated that a targeted workflow could be applied to multiplexed quantitation of proteins in human plasma with high reproducibility and high confidence in the results.

The impact of the paper resulted in broad adoption of the MRM technique around the world to accelerate the verification and validation of putative protein biomarkers, generating more than 800 citations, according to Google Scholar. Less than a decade after this important work, most proteomics laboratories today use a triple quadrupole-based mass spectrometer to perform MRM analysis.

“We congratulate Dr. Christie Hunter on receiving such a prestigious award from HUPO in recognition of her significant contributions to the rise of targeted proteomics as a viable technique to advance biomarker research,” said Dave Hicks, Vice President and General Manager of the Pharmaceutical and Academic Business at AB SCIEX.

“Dr. Hunter and her AB SCIEX colleagues continue to participate in exciting collaborations with leading proteomics researchers around the world to drive new innovations in software, chemistries and instrumentation that further expand quantitative proteomics workflows for the growing community of mass spectrometry users at large,” added Hicks.

Currently, Dr. Hunter is playing a pivotal role in the development of higher specificity workflows for targeted protein quantitation to overcome situations where sensitivity is limited by interferences or background. She is involved in the investigation of the utility of differential mobility separations for added selectivity of quantitation of peptides in complex mixtures. She is also working to enhance data-independent acquisition strategies, such as SWATHTM Acquisition, for quantitative proteomics to increase the multiplexing and reproducibility that can be achieved in a single experiment.

Source: AB SCIEX

Abcodia Licenses the ‘Risk of Ovarian Cancer Algorithm’ (ROCA) Developed at Massachusetts General Hospital and Queen Mary, University of London

Abcodia, the biomarker validation company with a focus on screening for cancer, today announced that it has entered into an agreement for an exclusive world-wide commercial license to the Risk of Ovarian Cancer Algorithm (ROCA) developed at Massachusetts General Hospital (MGH) and Queen Mary, University of London.

ROCA has the potential to be a major breakthrough for the early diagnosis of ovarian cancer. The diagnosis of ovarian cancer is usually made when the disease has spread outside the ovaries and as a result the outcome is poor. In the 80% of cases of ovarian cancer in which diagnosis occurs in the later stages, the 5-year survival rate is less than 20%. If diagnosed early, 5-year survival exceeds 85%. Hence the need for early diagnosis, in the hope that current treatments will be more effective. Around the world, an estimated 200,000 new cases of ovarian cancer are diagnosed in women each year and there are over 125,000 deaths.

ROCA is a test being validated for the screening of ovarian cancer. It was invented by Professor Ian Jacobs, Dean & Head School of Medicine, Faculty of Medical & Human Sciences, University of Manchester, and formerly of Queen Mary, University of London, and Dr Steven Skates of the Biostatistics Center, MGH, who together studied longitudinal patterns of CA125 in multiple cohorts of post-menopausal women to develop a statistical algorithm efficiently combining information in age and serial CA125 levels. ROCA has since shown excellent specificity, Positive Predictive Value (PPV) and sensitivity in large studies including UKCTOCS (UK Collaborative Trial of Ovarian Cancer Screening) and UKFOCSS (UK Familial Ovarian Cancer Screening Study).

A recent study by the MD Anderson Cancer Center in normal risk postmenopausal women reported a specificity of 99.9% and a PPV of 40% for ROCA when ultrasound was used as a secondary test. This confirms, in a USA population, results previously reported by the larger UKCTOCS trial involving 202,000 normal risk postmenopausal women. The published results from UKCTOCS2 indicate that, as well as achieving high specificity and PPV, ROCA can achieve a sensitivity of 89% for screen detection of ovarian cancer. UKCTOCS is a randomised trial comparing screening with standard care, and in 2015 will provide results on the impact of screening with ROCA on mortality and survival from ovarian cancer. The final data from UKCTOCS will be of great importance in guiding future clinical use of the ROCA in clinical practice.

Commenting on the recent MD Anderson publication, Professor Ian Jacobs, also Director of the UKCTOCS trial, said: “I am delighted to see the outcome of the MD Anderson 11 year study. The results reassuringly confirm in a USA setting those reported from the UKCTOCS prevalence study published in 2009. We now await further data from UKCTOCS in 2015 to establish whether the encouraging specificity and sensitivity data translate into improvements in survival and mortality which through early detection can help women affected by ovarian cancer.”

Dr Julie Barnes, Abcodia’s CEO, said: “The licensing of ROCA is a significant opportunity for Abcodia and we now intend to work with the co-founders to actively plan a commercialisation path that will in due course enable ROCA to be made available to women in Europe, US and around the world. We are currently in active discussions with partners in different territories to support our mission. Based on the reports to date, and in particular the sensitivity, specificity and PPV data, we will begin to explore ways in which the ROCA could be implemented in clinical practice. The eventual clinical use will of course be informed and guided by the outcome of UKCTOCS and other clinical trials.”

Source: Abcodia

MicroRNAs have diagnostic and prognostic potential in urinary bladder cancer

German researchers have identified four biomarkers that correctly determine malignancy of urinary bladder cancers and contribute to the accurate prediction of patient outcomes. Their results are published in the September issue of The Journal of Molecular Diagnostics.

Current prognosticators of bladder cancer, such as tumor grade, stage, size, and number of foci, have limited usefulness for clinicians since they do not accurately reflect clinical outcomes. Therefore, investigators have been searching for new biomarkers with better diagnostic and prognostic capabilities. Focusing on the role of microRNAs (miRNAs), small non-coding RNAs, researchers have identified four miRNAs that together perfectly discriminated between nonmalignant and malignant tissue, including one alone that classified 81% of the samples correctly. Levels of two miRNAs correlated with overall survival time.

Urinary bladder cancer is the fourth most common cancer in the West. According to the National Cancer Institute, it is estimated that in the United States 72,570 individuals will be diagnosed with and 15,210 will die of cancer of the urinary bladder in 2013. At presentation, in 75% of patients the cancers are confined to the mucosa or submucosa (known as non-muscle invasive bladder cancer, NMIBC), whereas in 25% of cases the cancers have already invaded nearby muscle (muscle-invasive bladder cancer, MIBC).

In a series of experiments, investigators analyzed bladder tissue from patients with NMIBC, MIBC, and nonmalignant bladders. After screening 723 miRNAs by microarray, they selected a subset of 15 distinctively deregulated miRNAs for further validation by real-time quantitative PCR. Seven miRNAs were found to be up-regulated, and eight were down-regulated in malignant bladder tissue samples compared to healthy tissue. Four miRNAs were expressed differently in bladder cancers that invaded muscle compared to those that did not. With one exception, no correlation was found between tumor stage and miRNA levels.

When all 15 of the selected miRNAs were considered together, they correctly classified 100% of tissues as either normal or malignant. Further analysis identified four miRNAs that led to 100% correct classification, and one miRNA (miR-130b) that by itself had an 81% accuracy rate. “These results underline the great potential of miRNAs to serve as diagnostic markers, as previously noted for other urological tumors,” says lead investigator Klaus Jung, MD, the Department of Urology at the University Hospital Charité, Berlin and the Berlin Institute for Urologic Research.

The investigators found that tumor grading could not be correlated with overall survival. Yet, they were able to find two miRNAs that significantly correlated with survival: miR-141 and miR-205. miR-141 showed a trend (P=0.08) of being able to stratify patients with muscle-invasive tumors into two groups with different overall survival times. “This finding could be of clinical importance, but these results must be interpreted cautiously,” says Dr. Jung. “However, previously published studies underline the possible prognostic potential of miRNAs to predict progression and disease-specific or overall survival in bladder cancer patients.”

miRNAs are small non-coding RNAs that contain between 19 and 24 nucleotides. miRNAs regulate gene expression by degrading messenger RNAs or impairing their translation. In recent years there has been a growing interest in miRNAs as potential diagnostic and/or prognostic biomarkers in cancers and other diseases.

Study: miRNA Profiling Identifies Candidate miRNAs for Bladder Cancer Diagnosis and Clinical Outcome [The Journal of Molecular Diagnostics]

Source: EurekAlert!